New approach to cancer therapy: heparin binding-epidermal growth factor-like growth factor as a novel targeting molecule.

Heparin binding-epidermal growth factor-like growth factor (HB-EGF) is one of the EGF receptor ligands and possesses several functional domains. It is involved in diverse biological processes, including wound healing, blast implantation, atherosclerosis and tumor formation, through its interactions with various molecules. We have reported that HB-EGF gene expression is significantly elevated in human ovarian cancer, and further demonstrated that HB-EGF plays key roles in the acquisition of malignant phenotypes, such as cell survival in peritoneal fluid, cell adhesion on extracellular matrices, invasion, angiogenesis, tumorigenicity, and chemoresistance in ovarian cancer. Thus, HB-EGF was considered as a promising target for cancer therapy. In vitro as well as in vivo experiments have revealed that cross-reacting material 197 (CRMI97), a specific inhibitor of HB-EGF, or a small interfering RNA for HB-EGF can block each step involved in peritoneal dissemination. According to these pieces of evidence, the development of targeting tools against HB-EGF, such as CRM197, could allow us to improve the prognosis of cancer patients.